Depression affects more than 15 million Americans in a given year. Compared to physical health, less is known about the affect of diet quality on symptoms of depression. In this study, we investigated the relationship between diet quality and reported symptoms of depression in a low-income urban population. Subjects included 1,118 African-American and white adults, aged 30 to 64 years, living in Baltimore, MD, and represented a subsample of the initial examination and recruitment phase of the Healthy Aging in Neighborhoods of Diversity across the Life Span study. Nutrition data were based on two 24-hour dietary recalls collected by trained interviewers using the US Department of Agriculture Automated Multiple Pass Method. Diet quality was calculated using the US Department of Agriculture Healthy Eating Index (HEI)-2005. Depressive symptoms were assessed by trained interviewers using the Center for Epidemiologic Studies Depression scale. We used both linear and logistic regression analyses to examine whether diet quality was associated with depressive symptoms. The dependent variable was depressive symptoms and independent variables included HEI-2005, race, sex, age, education, income, and food-assistance program participation. The mean HEI-2005 score was 52.17+/-0.40 (out of 100). The mean Center for Epidemiologic Studies Depression scale score was 11.64+/-0.25 (out of 40). Diet quality was significantly associated with reported symptoms of depression. However, income was a significantly stronger predictor of depression compared to diet quality, education, and sex. These data suggest that registered dietitians should be aware of relationships between psychological status and nutritional health when assisting clients to better manage their food choices to improve their overall health and quality of life. Folate deficiency has been implicated in the etiology of unipolar depression. In this study, we attempted to cross-link plasma folate, depressive symptoms, and dietary quality (or dietary intake of folate) together in a comprehensive framework, while examining effect modification of those associations by sex. This was a cross-sectional, population-based study of 1681 participants aged 30-64 y (Healthy Aging in Neighborhoods of Diversity across the Lifespan Study). Participants were administered the Center for Epidemiologic Studies Depression scale (CES-D). Measures of plasma folate and dietary intakes (2 24-h recalls) from which the 2005-Healthy Eating Index (HEI) was computed were available. Multivariate logistic regression and structural equation modeling (SM) were conducted. Compared with the lowest tertile, the middle and uppermost tertiles of plasma folate were associated with a 39-40% reduced odds of elevated CES-D (>or =16) among women adjusted odds ratio (T(3) vs. T(1)) = 0.60 (95% CI = 0.42-0.86);P = 0.006. Confounding of this association by HEI(total) was noted among both men and women, although dietary folate did not confound this association appreciably. In SM, plasma folate completely mediated the inverse HEI(total)-CES-D association among men only, specifically for HEI(2) (higher intakes of whole fruits), HEI(3) (total vegetables), HEI(5) (total grains), HEI(6) (whole grains), HEI(7) (milk), and HEI(12) (lower discretionary energy). Among women, HEI(total) and 4 components had an inverse direct effect on CES-D score, suggesting a mechanism that is independent of plasma folate. Depressive symptoms in our study may be alleviated by improving overall dietary quality, with plasma folate playing a potential mediating role only among men.